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Objective To assess the association of polymorphism at rs12645561 locus of Nei endonuclease Ⅷ-like 3 ( NEIL3) gene with the severity of coronary atherosclerosis in Han population of Hubei and Henan regions in central China. Methods In 947 cases undergoing coronary angiography, the severity of coronary atherosclerosis was calculated by lesion vessel number scores and Gensini scores.The genotypes of rs12645561 were analyzed by high resolution melting curve. The plasma NEIL3 levels were measured by en-zyme-linked immunosorbent assay. Results The minor allele T of rs12645561 was significantly associated with the risk of coronary ar-tery disease (χ2=12.165, P<0.05) including increased lesion vessel scores and Gensini scores (χ2=14.745 and 15.615,P<0.05). The variant risk genotypes ( CC+CT) of rs12645561, body mass index of more than 25 kg/m2 , hypelipidemia and smoking habit were all the independent risk factors for higher Gensini scores ( OR=1.50, 1.54, 2.01 and 1.42, respectively, P<0.05) . There were signifi-cantly inverse correlations of plasma NEIL3 levels with the distribution of rs12645561, lesion vessel number scores and Gensini scores ( P<0.05) . Conclusion rs12645561 may correlate with the severity of coronary atherosclerosis, and contribute to the development of coronary atherosclerosis of Han population of Henan and Hubei regions. rs12645561 may also affect the levels of NEIL3 protein.
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BACKGROUND: Osteoprotegerin (OPG) plays protective roles against the development of vascular calcification (VC) which greatly contributes to the increased cardiovascular events in patients with chronic kidney disease (CKD). The present study aimed to find the non-traditional, kidney-related cardiovascular risk factors correlated to serum OPG and the effect of serum OPG on the arterial stiffness measured by brachial ankle pulse wave velocity (baPWV) in patients with the pre-dialysis CKD. METHODS: We cross-sectionally analyzed the data from the patients in whom baPWV and the serum OPG were measured at the time of enrollment in a prospective pre-dialysis CKD cohort study in Korea. RESULTS: Along with traditional cardiovascular risk factors such as age, diabetes mellitus, pulse pressure, and baPWV, non-traditional, kidney-related factors such as albuminuria, plasma level of hemoglobin, total CO2 content, alkaline phosphatase, and corrected calcium were independent variables for serum OPG in multivariate linear regression. Reciprocally, the serum OPG was positively associated with baPWV in multivariate linear regression. The baPWV in the 3rd and 4th quartile groups of serum OPG were higher than that in the 1st quartile group after adjustments by age, sex and other significant factors for baPWV in linear mixed model. CONCLUSION: Non-traditional, kidney-related cardiovascular risk factors in addition to traditional cardiovascular risk factors were related to serum level of OPG in CKD. Serum OPG level was significantly related to baPWV. Our study suggests that kidney-related factors involved in CKD-specific pathways for VC play a role in the increased secretion of OPG into circulation in patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01630486